PMID- 34837787
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 1873-4243 (Electronic)
IS  - 1093-3263 (Linking)
VI  - 111
DP  - 2022 Mar
TI  - In-silico design of peptides for inhibition of HLA-A*03-KLIETYFSK complex as a 
      new drug design for treatment of multiples sclerosis disease.
PG  - 108079
LID - S1093-3263(21)00250-3 [pii]
LID - 10.1016/j.jmgm.2021.108079 [doi]
AB  - Multiple sclerosis is recognized as a chronic inflammatory disease. Human 
      leukocyte antigen (HLA) plays an important role in initiating adaptive immune 
      responses. HLA class I is present in almost all nucleated cells and presents the 
      cleaved endogenous peptide antigens to cytotoxic T cells. HLA-A*03 is one of the 
      HLA class I alleles, which is reported as substantially related HLA to MS 
      disease. In 2011, the structure of the HLA-A*03 in complex was identified with an 
      immunodominant proteolipid protein (PLP) epitope (KLIETYFSK). This complex has 
      been reported as an important autoantigen-presenting complex in MS pathogenesis. 
      In this study, new peptides were designed to bind to this complex that may 
      prevent specific pathogenic cytotoxic T cell binding to this 
      autoantigen-presenting complex and CNS demyelination. Herein, 14 new helical 
      peptides containing 19 amino acids were designed and their structures were 
      predicted using the PEP-FOLD server. The binding of each designed peptide to the 
      mentioned complex was then performed. A mutation approach was used by the 
      BeAtMuSiC server to improve the binding affinity of the designed peptide. In each 
      position, amino acid substitutions leading to an increase in the binding affinity 
      of the peptide to the mentioned complex were determined. Finally, the resulting 
      complexes were simulated for 40 ns using AMBER18 software. The results revealed 
      that out of 14 designed peptides, "WRYWWKDWAKQFRQFYRWF" peptide exhibited the 
      highest affinity for binding to the mentioned complex. This peptide can be 
      considered as a potential drug to control multiple sclerosis disease in patients 
      carrying the HLA-A*03 allele.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Ghobadi, Zahra
AU  - Ghobadi Z
AD  - Department of Biology, Faculty of Basic Sciences, Shahrekord University, 
      Shahrekord, Iran.
FAU - Mahnam, Karim
AU  - Mahnam K
AD  - Department of Biology, Faculty of Basic Sciences, Shahrekord University, 
      Shahrekord, Iran; Nanotechnology Research Center, Shahrekord University, 
      Shahrekord, Iran. Electronic address: mahnam.karim@sku.ac.ir.
FAU - Shakhsi-Niaei, Mostafa
AU  - Shakhsi-Niaei M
AD  - Department of Genetics, Faculty of Basic Sciences, Shahrekord University, 
      Shahrekord, Iran.
LA  - eng
PT  - Journal Article
DEP - 20211116
PL  - United States
TA  - J Mol Graph Model
JT  - Journal of molecular graphics & modelling
JID - 9716237
RN  - 0 (HLA-A Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Drug Design
MH  - *HLA-A Antigens
MH  - Humans
MH  - *Multiple Sclerosis/drug therapy
MH  - Peptides
MH  - Sclerosis
OTO - NOTNLM
OT  - HLA-A*03
OT  - MM/GBSA Binding free energy
OT  - Molecular dynamics simulation
OT  - Multiple sclerosis
OT  - Peptide design
OT  - T cell receptor (TCR)
EDAT- 2021/11/28 06:00
MHDA- 2022/02/01 06:00
CRDT- 2021/11/27 20:08
PHST- 2021/09/01 00:00 [received]
PHST- 2021/11/03 00:00 [revised]
PHST- 2021/11/14 00:00 [accepted]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/11/27 20:08 [entrez]
AID - S1093-3263(21)00250-3 [pii]
AID - 10.1016/j.jmgm.2021.108079 [doi]
PST - ppublish
SO  - J Mol Graph Model. 2022 Mar;111:108079. doi: 10.1016/j.jmgm.2021.108079. Epub 
      2021 Nov 16.